The present invention relates to the art of mass spectroscopy, and in particular, to a method and system for high sensitivity, rapid, high efficiency mass spectroscopy.
It is known in the field of mass spectroscopy to provide spectrometers with an elongated conductor having multipole conductors which act as ion transmitters. In PCT Publication WO 99/38185 (the contents of which is incorporated herein by reference), a method and apparatus are disclosed for providing ion transmission between an ion source and a spectrometer. The ion transmission device includes a multipole rod set and a damping gas which dampens spatial and energy spreads of ions generated by a pulsed ion source. The multipole rod set has the effect of guiding the ions along an ion path so that they can be directed to the inlet of a mass spectrometer.
The WO ""185 publication discloses a MALDI (matrix-assisted laser desorption/ionization) ion source for producing a small jet of matrix and analyte molecules and ions and which have a wide range of energy spreads. The ion transmission device of WO ""185 spreads out the generated ions along the multipole ion guide axis to provide a quasi-continuous beam while i) reducing the energy spread of ions emitted from the source and ii) at least partially suppressing unwanted fragmented analyte ions. These ions are delivered to a time-of-flight spectrometer or other spectrometers.
The apparatus described in WO ""185 provides that single multiple rod sets or two or more rod sets can be used. Regardless of the number of rod sets used or the number of rods provided therein, the conductors merely provide ion guidance and possible energy damping by way of collision with a damping gas within the ion guide itself. No provision is made to enhance the efficiency or improve the speed of movement while retaining integrity of the ion beam sent to a mass spectrometer.
Another disclosure, U.S. Pat. No. 6,111,250 to Thomson, et al., discloses a mass spectrometer which includes rod sets constructed to create an axial field, e.g., a DC axial field. The Thomson, et al. ""250 disclosure provides for speeding the passage of ions through an ion guide and causing the ions to be fragmented. The ion source is disclosed as being an electrospray or ion spray device such as those described in U.S. Pat. Nos. 4,935,624 and 4,861,988, or a corona discharge needle or a plasma, as shown in U.S. Pat. No. 4,861,965. The ions are directed and their speed controlled for introduction into a xe2x80x9ctime-of-flightxe2x80x9d mass analyzer. In one embodiment, Thomson, et al. disclose the use of a set of auxiliary rods in combination with a set of quadrupole rods for the purpose of, among other things, introducing very low energy ions into a quadrupole mass analyzer. There is no disclosure by Thomson, et al. regarding transmitting intact analyte ions as a substantially continuous ion beam for highly sensitive, rapid mass analysis.
While there are numerous disclosures relating to the art of mass spectroscopy of analyte ions, there is an ever increasing demand for high speed and accurate mass spectroscopy of specimens, especially dilute specimens having only trace amounts of analyte ions. It is the purpose of the present invention to meet this and other needs in the art of mass spectroscopy.
The present invention is a method and system for determining the ratio of mass to charge of an analyte ion. According to the present invention, intact analyte ions are prepared from a sample by pulse ionizing using a pulse ionizer, e.g., preferably by matrix-assisted laser desorption/ionization (MALDI).
The present invention further includes simultaneously damping and linearly accelerating intact ions in a co-linear ion guide/accelerator to reduce the energy spread of the ions without fragmenting them and to linearly accelerate the ions to provide a substantially continuous beam of intact ions. This dual functionality step of the process in the system is implemented by co-linearly arranged multipole rods and accelerator rods which define an axial ion path along which the continuous ion beam travels. This step of the process and the system also includes a damping gas which acts to reduce the energy spread of the ions. While the pressure of the damping gas can range from 0.1 mTorr to 10 Torr, it is preferably from about 10 mTorr to about 1000 mTorr, and most preferably from about 50 mTorr to about 100 mTorr.
In a preferred embodiment of the present process and system, an additional ion guide can be provided for receipt of the ion beam resulting from the simultaneous damping and linear acceleration and further directing such beam to mass analysis. Preferably the additional ion guide is provided with a multipole ion guide having at least about eight ion guide rods.
Finally, the present invention includes a determination of mass to charge ratio of the substantially intact analyte ions provided from the previous step(s). In a preferred embodiment the determination of mass to charge ratio is conducted in an ion trap spectrometer. The invention is ideally suited for high-efficiency rapid ion trap spectroscopy.
The present invention provides a highly sensitive instrument for detection of analyte ions, e.g., peptides, in a concentration at the subfemtomole level. The present invention provides true MSMS capabilities which enable one to perform multiple MSMS experiments within very short periods of time. Moreover, the process and system of the present invention provide a high degree of accuracy even at extremely diluted levels and at unexpectedly high speed.
For a better understanding of the present invention, together with other and further objects, reference is made to the following description, taken in conjunction with the accompanying drawings, and its scope will be pointed out in the claims which follow.